Clobazam (DB00349): A Comprehensive Monograph

I. Executive Summary & Drug Identification

Clobazam is a small molecule drug belonging to the 1,5-benzodiazepine class, functioning as a positive allosteric modulator of the gamma-aminobutyric acid type A (GABAA​) receptor. Its primary, FDA-approved indication is for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in patients two years of age and older.[1] Synthesized in the 1960s, clobazam has a long history of use globally as both an anxiolytic and an anticonvulsant. Its unique 1,5-benzodiazepine structure confers a distinct pharmacological profile, most notably a reduced sedative potential compared to traditional 1,4-benzodiazepines.[1] This is attributed to a preferential affinity for the

GABAA​ receptor α2​ subunit, which mediates anxiolytic and anticonvulsant effects, over the α1​ subunit associated with sedation.[1] The drug is extensively metabolized in the liver, primarily by cytochrome P450 (CYP) enzymes, to its major active metabolite, N-desmethylclobazam (norclobazam). This metabolite contributes significantly to the overall therapeutic effect and possesses a substantially longer elimination half-life than the parent compound, a critical factor in the drug's clinical pharmacology, time to steady state, and withdrawal management.[5] Clobazam is a DEA Schedule IV controlled substance, reflecting its potential for abuse, misuse, and dependence.[1]

The extensive catalog of identifiers associated with clobazam reflects its long history and comprehensive study across numerous chemical, biological, and clinical databases. This breadth of data underscores its well-established nature as a therapeutic agent, even though its specific approval by the U.S. Food and Drug Administration (FDA) for LGS is relatively recent, positioning it as a well-characterized compound repurposed for a critical, high-need indication.[1]